OP0217 ANTI-RO52 ANTIBODIES ARE ASSOCIATED WITH HIGHER DISEASE SEVERITY IN PATIENTS WITH SJÖGREN DISEASE THROUGH ACTIVATION OF THE INTERFERON PATHWAY
Authors: E. Bettacchioli, A. Saraux, A. Tison, D. Cornec, M. Dueymes, N. Foulquier, S. Hillion, A. M. Roguedas-Contios, A. A. Benyoussef, M. Alarcon-Riquelme, J. O. Pers, V. Devauchelle-Pensec
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The diagnosis of primary Sjögren Disease (SjD) is currently based on a combination of clinical, histological and biological findings [1]. Current thinking supports anti-Ro60 antibodies as the most specific serum marker, while the impact of anti-Ro52 remains unclear [2]. <h3>Objectives</h3> The aim of this study was to characterize the clinical, serological, biological, transcriptomic and interferon profiles of SjD patients according to their anti-Ro52 status and discuss the role of anti-Ro52 in the prognosis of SjD. <h3>Methods</h3> SjD patients were recruited from the European PRECISESADS (378 patients) [3] and the independant Brittany DIApSS cohorts (160 patients) [4]. Four groups were defined: double negative (Ro52<sup>-</sup>/Ro60<sup>-</sup>), isolated anti-Ro52 positive (Ro52<sup>+</sup>), isolated anti-Ro60 positive (Ro60<sup>+</sup>), and double positive (Ro52<sup>+</sup>/Ro60<sup>+</sup>) patients. Clinical information, disease activity, and biological markers linked to disease severity were evaluated. Transcriptome data on whole blood by RNAseq and Type I and type II interferon signatures [5,6] were analyzed for PRECISESADS SjD patients. <h3>Results</h3> In both cohorts, arthritis, parotidomegaly, and biological markers (hypergammaglobulinemia, rheumatoid factor and inflammation) [7] were significantly more frequent in the double positive group as compared to other groups. ESSDAI, a score representing systemic activity [8], was also significantly higher in double positive patients compared to the others. Transcriptome analysis demonstrated that anti-Ro52 positivity was associated with a strong interferon pathway activation as the lead cause to explain the clinical associations. <h3>Conclusion</h3> Taken together, these results suggest that SjD patients with anti-Ro52 positivity adopt a more severe phenotype as compared to their negative counterparts, independently of anti-Ro60 positivity. <h3>References</h3> [1]Brito-Zerón P, Baldini C, Bootsma H, Bowman SJ, Jonsson R, Mariette X, et al. Sjögren syndrome. Nat Rev Dis Primer. 2016 Jul 7;2(1):1–20. [2]Decker P, Moulinet T, Pontille F, Cravat M, De Carvalho Bittencourt M, Jaussaud R. An updated review of anti-Ro52 (TRIM21) antibodies impact in connective tissue diseases clinical management. Autoimmun Rev. 2022 Mar;21(3):103013. [3]Soret P, Le Dantec C, Desvaux E, Foulquier N, Chassagnol B, Hubert S, et al. A new molecular classification to drive precision treatment strategies in primary Sjögren's syndrome. Nat Commun. 2021 Jun 10;12(1):3523. [4]Cornec D, Jousse-Joulin S, Pers JO, Marhadour T, Cochener B, Boisramé-Gastrin S, et al. Contribution of salivary gland ultrasonography to the diagnosis of Sjögren's syndrome: toward new diagnostic criteria? Arthritis Rheum. 2013 Jan;65(1):216–25. [5]Kirou KA, Lee C, George S, Louca K, Papagiannis IG, Peterson MGE, et al. Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Arthritis Rheum. 2004 Dec;50(12):3958–67. [6]Chiche L, Jourde-Chiche N, Whalen E, Presnell S, Gersuk V, Dang K, et al. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol Hoboken NJ. 2014 Jun;66(6):1583–95. [7]Baldini C, Pepe P, Quartuccio L, Priori R, Bartoloni E, Alunno A, et al. Primary Sjögren's syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology. 2014 May 1;53(5):839–44. [8]Brito-Zerón P, Kostov B, Solans R, Fraile G, Suárez-Cuervo C, Casanovas A, et al. Systemic activity and mortality in primary Sjögren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients. Ann Rheum Dis. 2016 Feb;75(2):348–55. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.